Interfacing Functional Systems - NCCR MSE

Interfacing Functional Systems

The objective of this project is to move beyond primary systems to maximize complexity and cumulate emergent properties that are a) significant (conceptual or practical), b) absent in the individual components, and c) inaccessible otherwise.

Ongoing projects focus on the development of orthogonal dynamic covalent bonds for advanced systems interfacing; current emphasis is on boronic esters from bioadhesives.  A second specific objective is the creation of artificial enzymes that operate with interactions that are new-to-nature; current emphasis is on the interfacing of anion-π interactions and streptavidin mutant libraries. A third specific objective focuses on disulfide exchange chemistry on cell surfaces to interface living cells with functional systems such as protein complexes involved in gene editing, artificial metalloenzymes for metabolic engineering, and liposomes or polymersomes as artificial organelles. In this project, emphasis is exclusively on added value from collaborations within the network of this NCCR, i.e., research that could not be realized without this NCCR. 

Scientific Highlights

  • The creation of the first anion-π enzyme: In sharp contrast to the ubiquitous cation-π catalysis in biology, anion-π catalysis, that is the stabilization of anionic transitions states on π-acidic aromatic surfaces, has been just been introduced in chemistry and has so far been unknown in biological systems.The creation of the first artificial enzyme that operates with anion-π interactions became possible by combining expertise from the Ward group on streptavidin mutant libraries and expertise from the Matile group on anion-π catalysis.  The emergent properties obtained from systems interfacing are fully selective catalysis of intrinsically disfavoured but biologically most relevant enolate chemistry, no trace of the intrinsically favoured but irrelevant product, and enantioselectivity near perfection (95% ee).

  • The discovery of the third orthogonal dynamic covalent bond: So far, only disulfide exchange under basic and hydrozane exchange under acidic conditions could be operated independently.  The combination of expertise from the Gademann group on bioadhesives and the Matile group on dynamic covalent surface architectures has lead to the introduction of boronic esters that can exchange independently from disulfides under and hydrozanes.  The availability of a third orthogonal dynamic covalent bond is of fundamental interest for systems interfacing.

Publications

E. Bartolami, D. Basagiannis, L. Zong, R. Martinent, Y. Okamoto, Q. Laurent, T. R. Ward, M. Gonzalez-Gaitan, N. Sakai, S. Matile “Diselenolane-Mediated Cellular Uptake: Efficient Cytosolic Delivery of Probes, Peptides, Proteins, Artificial Metalloenzymes and Protein-Coated Quantum Dots“ Chem. Eur. J. 2019. [DOI]
A. Goujon, A. Colom, K. Straková, V. Mercier, D. Mahecic, S. Manley, N. Sakai, A. Roux, S. Matile “Mechanosensitive Fluorescent Probes to Image Membrane Tension in Mitochondria, Endoplasmic Reticulum, and Lysosomes“ J. Am. Chem. Soc. 2019. [DOI]
Q. Laurent, N. Sakai, S. Matile “The Opening of 1,2-Dithiolanes and 1,2-Diselenolanes: Regioselectivity, Rearrangements, and Consequences for Poly(disulfide)s, Cellular Uptake and Pyruvate Dehydrogenase Complexes“ Helv. Chim. Acta 2019. [DOI]
L. M. Lee, M. Tsemperouli, A. I. Poblador-Bahamonde, S. Benz, N. Sakai, K. Sugihara, S. Matile “Anion Transport with Pnictogen Bonds in Direct Comparison with Chalcogen and Halogen Bonds“ J. Am. Chem. Soc. 2019. [DOI]
X. Zhang, X. Hao, L. Liu, A. Pham, J. López-Andarias, A. Frontera, N. Sakai, S. Matile “Primary Anion−π Catalysis and Autocatalysis“ J. Am. Chem. Soc. 2018, 140(51):17867-17871. [DOI]
A. Goujon, K. Straková, N. Sakai, S. Matile “Streptavidin interfacing as a general strategy to localize fluorescent membrane tension probes in cells“ Chem. Sci. 2018. [DOI]
Y. Zhao, Y. Cotelle, L. Liu, J. López-Andarias, A. Bornhof, M. Akamatsu, N. Sakai, S. Matile “The Emergence of Anion−π Catalysis“ Acc. Chem. Res. 2018, 51(9):2255-2263. [DOI]
N. Sakai, S. Matile “Conjugated Polyimine Dynamers as Phase-Sensitive Membrane Probes“ J. Am. Chem. Soc. 2018. [DOI]
A. Colom, E. Derivery, S. Soleimanpour, C. Tomba, M. D. Molin, N. Sakai, M. González-Gaitán, S. Matile, A. Roux “A fluorescent membrane tension probe“ Nat. Chem. 2018. [DOI]
S. Matile “Chalcogen-Bonding Catalysis: From Neutral to Cationic Benzodiselenazole Scaffolds“ 2018. [DOI]
H. V. Humeniuk, A. Rosspeintner, G. Licari, V. Kilin, L. Bonacina, E. Vauthey, N. Sakai, S. Matile “White‐Fluorescent Dual‐Emission Mechanosensitive Membrane Probes that Function by Bending Rather than Twisting“ Angew. Chem. Int. Ed. 2018. [DOI]
J. López‐Andarias, A. Bauzá, N. Sakai, A. Frontera, S. Matile “Remote Control of Anion–π Catalysis on Fullerene‐Centered Catalytic Triads“ Angewandte Chemie International Edition 2018. [DOI]
Y. Okamoto, R. Kojima, F. Schwizer, E. Bartolami, T. Heinisch, S. MatileM. FusseneggerT. R. Ward “A cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell“ Nat. Commun. 2018. [DOI]
K. Strakova, S. Soleimanpour, M. Diez-Castellnou, N. Sakai, S. Matile “Ganglioside‐Selective Mechanosensitive Fluorescent Membrane Probes“ Helv. Chim. Acta 2018. [DOI]
M. Macchione, M. Tsemperouli, A. Goujon, A. R. Mallia, N. Sakai, K. Sugihara, S. Matile “Mechanosensitive Oligodithienothiophenes: Transmembrane Anion Transport Along Chalcogen‐Bonding Cascades“ 2018. [DOI]
A. Bornhof, A. Bauzá, A. Aster, M. Pupier, A. Frontera, E. Vauthey, N. Sakai, S. Matile “Synergistic Anion–(π)n–π Catalysis on π-Stacked Foldamers“ J. Am. Chem. Soc. 2018. [DOI]
S. B. Benz, A. I. Poblador‐Bahamonde, N. Low‐Ders, S. Matile “Catalysis with Pnictogen, Chalcogen, and Halogen Bonds“ Angew. Chem. Int. Ed. 2018. [DOI]
G. Licari, J. S. Beckwith, S. Soleimanpour, S. Matile, E. Vauthey “Detecting Order and Lateral Pressure at Biomimetic Interfaces Using a Mechanosensitive Second-Harmonic-Generation Probe“ Phys. Chem. Chem. Phys. 2018. [DOI]
X. Zhang, L. Liu, J. López-Andarias, C. Wang, N. Sakai, S. Matile “Anion-π Catalysis: Focus on Nonadjacent Stereocenters“ Helv. Chim. Acta 2018. [DOI]
P. Morelli, E. Bartolami, N. Sakai, S. Matile “Glycosylated Cell-Penetrating Poly(disulfide)s: Multifunctional Cellular Uptake at High Solubility“ Helv. Chim. Acta 2018, 101(1):e1700266. [DOI]
N. Chuard, A. I. Poblador-Bahamonde, L. Zong, E. Bartolami, J. Hildebrandt, W. Weigand, N. Sakai, S. Matile “Diselenolane-mediated cellular uptake“ 2018. [DOI]
M. M. Pellizzoni, F. Schwizer, C. W. Wood, V. Sabatino, Y. Cotelle, S. Matile, D. N. Woolfson, T. R. Ward “Chimeric Streptavidins as Host Proteins for Artificial Metalloenzymes“ ACS Catal. 2018. [DOI]
S. Benz, J. Mareda, C. Besnard, N. Sakai, S. Matile “Catalysis with chalcogen bonds: neutral benzodiselenazole scaffolds with high-precision selenium donors of variable strength“ Chem. Sci. 2017. [DOI]
J. López-Andarias, A. Frontera, S. Matile “Anion−π Catalysis on Fullerenes“ J. Am. Chem. Soc. 2017
L. Liu, Y. Cotelle, A. Bornhof, C. Besnard, N. Sakai, S. Matile “Anion–π Catalysis of Diels–Alder Reactions“ Angew. Chem. Int. Ed. 2017. [DOI]
C. Wang, S. Matile “Anion-π Catalysts with Axial Chirality“ Chem. Eur. J. 2017. [DOI]
E. Derivery, E. Bartolami, S. Matile, M. Gonzalez-Gaitan “Efficient Delivery of Quantum Dots into the Cytosol of Cells Using Cell-Penetrating Poly(disulfide)s“ J. Am. Chem. Soc. 2017. [DOI]
M. Akamatsu, N. Sakai, S. Matile “Electric-Field-Assisted Anion−π Catalysis“ J. Am. Chem. Soc. 2017, 139:6558-61. [DOI]
L. Liu, Y. Cotelle, J. Klehr, N. Sakai, T. R. WardS. Matile “Anion-π catalysis: bicyclic products with four contiguous stereogenic centers from otherwise elusive diastereospecific domino reactions on π-acidic surfaces“ Chem. Sci. 2017, 8:3770-74. [DOI]
S. MatileW. MeierC. G. Palivan “Strain-Promoted Thiol-Mediated Cellular Uptake of Giant Substrates: Liposomes and Polymersomes“ Angew. Chem. Int. Ed. 2017, 56:2947-50. [DOI]
P. Morelli, S. Matile “Sidechain Engineering in Cell-Penetrating Poly(disulfide)s“ Helv. Chim. Acta 2017, 100. [DOI]
M. Macchione, N. Chuard, N. Sakai, S. Matile “Planarizable Push–Pull Probes: Overtwisted Flipper Mechanophores“ ChemPlusChem 2017. [DOI]
Q. Verolet, M. Dal Molin, A. Colom, A. Roux, L. Guénée, N. Sakai, S. Matile “Twisted Push‐Pull Probes with Turn‐On Sulfide Donors“ Helv. Chim. Acta 2017, 100:e1600328. [DOI]
S. Soleimanpour, A. Colom, E. Derivery, M. Gonzalez-Gaitan, A. Roux, N. Sakai, S. Matile “Headgroup engineering in mechanosensitive membrane probes“ Chem. Commun. 2016, 52:14450-53. [DOI]
C. Wang, F. N. Miros, J. Mareda, N. Sakai, S. Matile “Asymmetric Anion–π Catalysis on Perylenediimides“ Angew. Chem. Int. Ed. 2016, 55:14422-26. [DOI]
N. Chuard, K. Fujisawa, P. Morelli, J. Saarbach, N. Winssinger, P. Metrangolo, G. Resnati, N. Sakai, S. Matile “Activation of Cell-Penetrating Peptides with Ionpair−π Interactions and Fluorophiles“ J. Am. Chem. Soc. 2016, 138:11264-71. [DOI]
S. Benz, M. Macchione, Q. Verolet, J. Mareda, N. Sakai, S. Matile “Anion Transport with Chalcogen Bonds“ J. Am. Chem. Soc. 2016, 138:9093-96. [DOI]
Y. Cotelle, N. Chuard, S. Lascano, V. Lebrun, R. Wehlauch, N. Bohni, S. Lörcher, V. Postupalenko, S. ReddyW. MeierC. G. Palivan, K. Gademann, T. R. WardS. Matile “Interfacing Functional Systems“ Chimia 2016, 6:418. [DOI]
W. Kelton, T. PeschS. MatileS. Reddy “Surveying the Delivery Methods of CRISPR/Cas9 for ex vivo Mammalian Cell Engineering“ Chimia 2016, 6:439. [DOI]
L. Liu, Y. Cotelle, A. Avestro, N. Sakai, S. Matile “Asymmetric Anion−π Catalysis of Iminium/Nitroaldol Cascades To Form Cyclohexane Rings with Five Stereogenic Centers Directly on π-Acidic Surfaces“ J. Am. Chem. Soc. 2016, 138:7876-79. [DOI]
A. Bolag, N. Sakai, S. Matile “Dipolar Photosystems: Engineering Oriented Push–Pull Components into Double- and Triple-Channel Surface Architectures“ Chem. Eur. J. 2016, 22:9006-14. [DOI]
L. Liu, S. Matile “Anion-π transaminase mimics“ Supramol. Chem. 2016:1-5. [DOI]
P. Morelli, X. Martin-Benlloch, R. Tessier, J. Waser, N. Sakai, S. Matile “Ethynyl benziodoxolones: functional terminators for cell-penetrating poly(disulfide)s“ Polym. Chem. 2016, 7:3465-70. [DOI]
Y. Cotelle, V. Lebrun, N. Sakai, T. R. WardS. Matile “Anion‑π Enzymes“ ACS Cent. Sci. 2016:DOI: 10.1021/acscentsci.6b00097. [DOI] [More Information]
S. Lascano, K. Zhang, R. Wehlauch, K. Gademann, N. Sakaiab, S. Matile “The third orthogonal dynamic covalent bond“ Chem. Sci. 2016, 7:4720. [DOI]
M. Akamatsu, S. Matile “Expanded Chiral Surfaces for Asymmetric Anion–π Catalysis“ Synlett 2016, 27:1041-46. [DOI]
Y. Zhao, Y. Cotelle, N. Sakai, S. Matile “Unorthodox Interactions at Work“ J. Am. Chem. Soc. 2016, 138:4270-77. [DOI]
Y. Cotelle, S. Benz, A. Avestro, T. R. Ward, N. Sakai, S. Matile “Anion-π Catalysis of Enolate Chemistry: Rigidified Leonard Turns as a General Motif to Run Reactions on Aromatic Surfaces“ Angew. Chem. Int. Ed. 2016, 55:4275. [DOI]
F. N. Miros, Y. Zhao, G. Sargsyan, M. Pupier, C. Besnard, C. Beuchat, J. Mareda, N. Sakai, S. Matile “Enolate Stabilization by Anion–π Interactions: Deuterium Exchange in Malonate Dilactones on π-Acidic Surfaces“ Chem. Eur. J. 2016, 22:2648-57. [DOI]
S. Benz, J. López‐Andarias, J. Mareda, N. Sakai, S. Matile “Catalysis with Chalcogen Bonds“ Angew. Chem. Int. Ed. 2016, 56:812-15. [DOI]
Q. Verolet, A. Rosspeintner, S. Soleimanpour, N. Sakai, E. Vauthey, S. Matile “Turn-On Sulfide π Donors: An Ultrafast Push for Twisted Mechanophores“ J. Am. Chem. Soc. 2015, 137:15644-47. [DOI]
G. Gasparini, S. Matile “Protein delivery with cell-penetrating poly(disulfide)s“ Chem. Commun. 2015, 51:17160-62. [DOI]
Y. Zhao, Y. Cotelle, A. J. Avestro, N. Sakai, S. Matile “Asymmetric Anion-π Catalysis: Enamine Addition to Nitroolefins on pi-Acidic Surfaces“ J. Am. Chem. Soc. 2015, 137:11582-85. [DOI]
K. Fujisawa, M. Humbert-Droz, R. Letrun, E. Vauthey, T. A. Wesolowski, N. Sakai, S. Matile “Ion Pair-π Interactions“ J. Am. Chem. Soc. 2015, 137:11047-56. [DOI]
K. D. Zhang, N. Sakai, S. Matile “Colorful surface architectures with three different types of dynamic covalent bonds: integration of anthocyanins, tritylium ions and flavins“ Org. Biomol. Chem. 2015, 13:8687-94. [DOI]
K. D. Zhang, S. Matile “Complex Functional Systems with Three Different Types of Dynamic Covalent Bonds“ Angew. Chem. Int. Ed. 2015, 54:8980-83. [DOI]
G. Gasparini, E. K. Bang, J. Montenegro, S. Matile “Cellular uptake: lessons from supramolecular organic chemistry“ Chem. Commun. 2015, 51:10389-402. [DOI]
G. Gasparini, G. Sargsyan, E. Bang, N. Sakai, S. Matile “Ring Tension Applied to Thiol‐Mediated Cellular Uptake“ Angew. Chem. Int. Ed. 2015, 54:7328-31. [DOI]
O. Yushchenko, G. Licari, S. Mosquera-Vazquez, N. Sakai, S. Matile, E. Vauthey “Ultrafast Intersystem-Crossing Dynamics and Breakdown of the Kasha-Vavilov's Rule of Naphthalenediimides“ J. Phys. Chem. Lett. 2015, 6:2096-100. [DOI]
Q. Verolet, S. Soleimanpour, K. Fujisawa, M. Dal Molin, N. Sakai, S. Matile “Design and Synthesis of Mixed Oligomers with Thiophenes, Dithienothiophene S, S‐Dioxides, Thieno [3, 4] pyrazines and 2, 1, 3‐Benzothiadiazoles: Flipper Screening for Mechanosensitive Systems“ ChemistryOpen 2015, 4:264-67. [DOI]
O. Yushchenko, D. Villamaina, N. Sakai, S. Matile, E. Vauthey “Comparison of Charge-Transfer Dynamics of Naphthalenediimide Triads in Solution and π-Stack Architectures on Solid Surfaces“ J. Phys. Chem. B 2015, 119:14999-15008. [DOI]
Y. Zhao, S. Benz, N. Sakai, S. Matile “Selective acceleration of disfavored enolate addition reactions by anion–π interactions“ Chem. Sci. 2015, 6:6219-23. [DOI]
J. Lopez-Andarias, A. Bolag, C. Nancoz, E. Vauthey, C. Atienza, N. Sakai, N. Martin, S. Matile “Electron-deficient fullerenes in triple-channel photosystems“ Chem. Commun. 2015, 51:7543-45. [DOI]
M. Dal Molin, Q. Verolet, S. Soleimanpour, S. Matile “Mechanosensitive membrane probes“ Chem. Eur. J. 2015, 21:6012-21. [DOI]
Y. Zhao, G. Huang, C. Besnard, J. Mareda, N. Sakai, S. Matile “Big, Strong, Neutral, Twisted, and Chiral π Acids“ Chem. Eur. J. 2015, 21:6202-07. [DOI]
N. Chuard, G. Gasparini, A. Roux, N. Sakai, S. Matile “Cell-penetrating poly(disulfide)s: the dependence of activity, depolymerization kinetics and intracellular localization on their length“ Org. Biomol. Chem. 2015, 13:64-7. [DOI]
K. Fujisawa, C. Beuchat, M. Humbert-Droz, A. Wilson, T. A. Wesolowski, J. Mareda, N. Sakai, S. Matile “Anion-π and cation-π interactions on the same surface“ Angew. Chem. Int. Ed. 2014, 53:11266-9. [DOI]
F. N. Miros, G. Huang, Y. Zhao, N. Sakai, S. Matile “Coumarin synthesis on π-acidic surfaces“ Supramol. Chem. 2014, 27:303-09. [DOI]
H. Hayashi, A. Sobczuk, A. Bolag, N. Sakai, S. Matile “Antiparallel three-component gradients in double-channel surface architectures“ Chem. Sci. 2014, 5:4610-14. [DOI]
A. V. Jentzsch, S. Matile “Anion transport with halogen bonds“ Halogen Bonding I 2014:205-39. [DOI]